This project intends to create a contact lens for ocular drug delivery that resolves key barriers to commercial feasibility. Contact lens drug delivery has been studied for many years, but technical challenges such as constant-rate release and controlled triggering have inhibited progress. Current prototypes release drugs at a decreasing rate, and undesirably begin releasing in storage solution (needed to keep the lens soft/wearable). A successful alternative would quickly replace topical eye drops as the treatment standard for open-angle glaucoma, which affects 2.8M Americans ($5B market) and can eventually lead to blindness. Drops have limited bioavailability (5-10% drug absorption due to burst dosage and ocular drainage) and patient compliance (20- 60% non-compliance due to tedious dosing schedule). We propose to create a silicone hydrogel contact lens with a dual-layer coating on the post-lens surface to give zero order release kinetics and protection against burst dosage failure. Also, zonal loading of drug ingredient (i.e., ring configuration) will allow targeting of specific areas active in disease. The specific aims of the Phase I proposal are: Aim 1: Novel dual-layer structure on post-lens surface to achieve near zero order drug release - We will synthesize a nanoporous polymer matrix (1st Layer), embed it with model drug (bimatoprost), and imprint it on the post-lens surface. We will cover this drug-loaded layer with a hydrophilic barrier coating (2nd Layer) that provides zero-order delivery, biocompatibility and burst failure protection. Milestones: Constant-rate drug release of bimatoprost over 24-hours. Phase II goal: Extending release time to 7 days, 30 days. Animal model to evaluate release kinetics, toxicity and efficacy. Aim 2: Hydrophilic barrier coating (2nd Layer) to control turnovr rate of post-lens tear film - Compared to ocular tear film, PLTF turnover is significantly slower, and thus advantageous to drug residence time. We will modify the post-lens surface to further stabilize the PLTF and maximize drug residence. Milestones: Produce a barrier coating on SiHy lens to reduce contact angle with simulated tear film to <15. Phase II goal: Animal model to compare PLTF turnover rate in animal model. Aim 3: Location-specific drug loading and delivery - We will zonally load the bimatoprost into the 1st Layer using a ring configuration with inner diameter 10mm (not residing in the optical pathway) and outer diameter up to 14mm (edge of the contact lens). We hypothesize location specificity to be clinically beneficial in concentrating drug on the ocular components that are active in disease or drug treatment (e.g. trabecular meshwork/Schlemm's canal in glaucoma), and understand this aspect of zonal drug loading on the contact lens to be novel. Milestones: Majority of drug (80%) lands within well-defined area of a model cornea, minimal unwanted outflow. Phase II goal: Animal model to demonstrate efficacy correlation to specific loading locations.